Leyton Cristian E, Cassidy Ben, Villemagne Victor L, Jones Gareth, Kwok John B, Rowe Christopher C, Ballard Kirrie J, Piguet Olivier, Hodges John R
Faculty of Health Sciences, The University of Sydney, Lidcombe; Neuroscience Research Australia Randwick; Australian Research Council Centre of Excellence in Cognition and its Disorders, Sydney, New South Wales, Australia.
Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jan;1(1):24-31. doi: 10.1016/j.bpsc.2015.09.004. Epub 2015 Oct 14.
Despite divergent clinical features, language and amnestic presentations of Alzheimer's disease (AD) appear to show comparable regional amyloid-β (Aβ) burden. By using a statistical network approach, we aimed to identify complex network patterns of Aβ deposition and explore the effect of apolipoprotein E (APOE) ε4 allele on cortical Aβ burden across AD phenotypes.
Sixteen amnestic AD participants and 18 cases with logopenic-variant of primary progressive aphasia (lv-PPA) with a high cortical Aβ burden were selected. A comprehensive clinical assessment, Aβ imaging, and APOE genotyping were performed in all cases. Statistical network analysis was undertaken based on the estimation of sparse partial correlations of Aβ burden between cortical regions. Global and regional network statistical parameters as well as the effect of APOEε4 genotype on cortical Aβ were explored.
The two groups showed equivalent distribution of cortical amyloid burden and frequency of APOEε4 genotype. Statistical network analysis, however, demonstrated divergent connectivity properties. The lv-PPA group demonstrated higher mean network degree and shorter characteristic path length than the amnestic AD group. Amnestic AD cases showed connectivity hubs confined to the mesial temporal and prefrontal lobes bilaterally, whereas lv-PPA cases showed hubs scattered across the whole cortical mantle. An interaction effect on total Aβ burden between APOE genotype and AD presentations was also detected.
The network analysis reveals interregional network differences not evident using a simple comparison of Aβ burden. This suggests that regional neurotoxic effects may explain the phenotypical differences in AD presentation and that these can be modulated by APOE genotype.
尽管阿尔茨海默病（AD）的临床特征、语言和记忆表现存在差异，但其区域淀粉样β蛋白（Aβ）负荷似乎具有可比性。我们旨在通过使用统计网络方法，识别Aβ沉积的复杂网络模式，并探讨载脂蛋白E（APOE）ε4等位基因对不同AD表型皮质Aβ负荷的影响。
选取16名遗忘型AD患者和18例皮质Aβ负荷较高的原发性进行性失语症（lv-PPA）语言变异型患者。对所有病例进行全面的临床评估、Aβ成像和APOE基因分型。基于皮质区域间Aβ负荷的稀疏偏相关性估计进行统计网络分析。探索全局和区域网络统计参数以及APOEε4基因型对皮质Aβ的影响。
两组的皮质淀粉样蛋白负荷分布和APOEε4基因型频率相当。然而，统计网络分析显示出不同的连接特性。与遗忘型AD组相比，lv-PPA组表现出更高的平均网络度和更短的特征路径长度。遗忘型AD病例的连接枢纽局限于双侧内侧颞叶和前额叶，而lv-PPA病例的枢纽则分散在整个皮质。还检测到APOE基因型与AD表现之间对总Aβ负荷的交互作用。
网络分析揭示了仅通过简单比较Aβ负荷不明显的区域间网络差异。这表明区域神经毒性作用可能解释了AD表现的表型差异，并且这些差异可由APOE基因型调节。
